Studies in HIV-infected individuals have reported changes in levels of surface expression of activation markers and naive / memory phenotypes on CD4+ and CD8+ cells. Specifically, HIV-infection results in a profound depletion of naive phenotype CD4+ and CD8+ T cells. These changes are related to the stage of HIV infection and may be predictive of progression to AIDS. Infection of sooty mangabeys with SIV results in persistent infection without immunodeficiency, whereas SIV infection in rhesus macaques results in AIDS. Since the outcome of SIV infection is so different among rhesus macaques and sooty mangabeys, we have analyzed differences in surface expression of these antigens on CD4+ and CD8+ cells during the course of SIV infection. Because of the differential expression of these memory markers on CD4+ and CD8+ T cells and the existence of CD8+ cells that do not express CD3, we developed a novel 4 color flow cytometric technique to precisely define memory and naive cells in CD4+ and CD8+ T cells. In uninfected animals examined to date, naive (CD45RA+ 62L+) cells account for approximately 25 - 60% of both CD4+ and CD8+ T cells. Interestingly, in an SIV-infected macaque analyzed 3-4 months after infection, naive phenotype CD4+ cells were increased (approx. 75%). This is an unexpected funding in light of studies in HIV-infected persons and one which will be addressed in expanded studies of SIV-infected macaques and mangabeys.